Recommendations for research

The guideline development group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future.

1 Service provision for neutropenic sepsis in patients with cancer

A prospective national cohort study should be carried out to assess the incidence of suspected and proven neutropenic sepsis in patients having anticancer treatment.

Why this is important

The incidence of suspected neutropenic sepsis in England and Wales is difficult to determine. A national cohort study of patients referred for suspected neutropenic sepsis, including diagnoses and clinical outcomes, should be undertaken to improve service planning and delivery. Such a study may also generate hypotheses concerning more and less efficient methods of delivering services for neutropenic sepsis, which could then be formally tested.

2 Patient support and information

A descriptive study involving patients who have had neutropenic sepsis and their carers should be undertaken to find out what types of support and information patients and carers were given, which of these they found helpful or unhelpful, and whether they think additional or different types of support or information are needed.

Why this is important

There is a lack of research on the experience of patients who have had neutropenic sepsis and their carers. Better knowledge of the support and information patients and carers are given, how helpful they find it and how they think it could be improved will allow the development of different approaches to providing information and support and test these in practice. This research could improve the experience of patients, and potentially their clinical outcomes. It may also highlight important inequities and suggest ways of addressing them.

3 Signs and symptoms that predict neutropenic sepsis in the community

A prospective study should be carried out to determine which signs and symptoms experienced by patients in the community predict neutropenic sepsis and the outcomes of these episodes.

Why this is important

The initial decision to refer to secondary or tertiary care for investigation for suspected neutropenic sepsis is an important step that has both risks and benefits. An overly inclusive approach will inconvenience many patients and carers, expose patients to unnecessary invasive testing and increase resource use by the health service. Referral criteria that are too narrow will delay the emergency treatment of infection and may lead to death, increased need for intensive or critical care facilities, and reduced overall quality of life for patients with cancer and their carers. The current research base in this area is weak and largely extrapolated from selected populations in hospitals. A clearer, quantitative understanding of how the features of neutropenic sepsis appear in patients may lead to more accurate referral criteria for suspected neutropenic sepsis.

4 Reducing the risk of complications of anticancer treatment in children and young people, and in adults diagnosed with lymphoma

Randomised studies should investigate primary prophylaxis of neutropenic sepsis in 2 populations: children and young people (aged under 18) having treatment for solid tumours or haematological malignancies, or stem cell transplantation; and adults (aged 18 and older) diagnosed with lymphoma. The studies should compare the effectiveness of fluoroquinolone antibiotics given alone, fluoroquinolone antibiotics given together with G-CSF preparations, and G-CSF preparations given alone. Outcome measures should include overall mortality, infectious episodes and adverse events. In addition, quality of life should be determined using quantitative and qualitative methods. The resulting data should be used to develop a cost-effectiveness analysis comparing these 3 forms of prophylaxis in children and young people having anticancer treatment, and in adults diagnosed with lymphoma.

Why this is important

Data from studies of adults with leukaemia, stem cell transplantation and many solid tumours suggest that prophylaxis with fluoroquinolone antibiotics reduces the risk of neutropenic sepsis. However, the benefit of fluoroquinolone antibiotics in adults diagnosed with lymphoma is unclear. Children and young people having anticancer treatment are a distinct population and differ from adults in a number of ways, including the types of cancer they have, the anticancer treatment they are given, their reactions to fluoroquinolones and subcutaneous injections, and the ease with which they can adhere to daily medication. The effects of these differences are not known, but it is known that death rates from neutropenic sepsis are higher in children and young people than in adults. Studies of primary prophylaxis of neutropenic sepsis in children and young adults, and in adults with lymphoma, could be of great value in helping to reduce the risk of neutropenic sepsis in these 2 patient populations.

5 Switching from inpatient intravenous to outpatient oral antibiotic therapy in patients with neutropenic sepsis

A randomised controlled trial should be undertaken to evaluate the clinical and cost effectiveness of stopping intravenous antibiotic therapy and switching to oral therapy within the first 24 hours of treatment in patients with neutropenic sepsis who are having treatment with intravenous antibiotics. The outcomes to be measured are overtreatment, death, need for critical care, length of hospital stay, duration of fever and quality of life.

Why this is important

Moderately strong evidence was found to support the use of outpatient therapies for patients with neutropenic sepsis who are at low risk of severe infection. These studies switched from inpatient to outpatient treatment at a variety of time points. A meta-regression undertaken by the Guideline Development Group suggested that very early (before 24 hours) discharge is associated with a greater risk of readmission and need to change treatments, but the evidence was sparse. If a short period of hospital admission was found to be safe and effective for selected patients with neutropenic sepsis, it could provide considerable improvements in their quality of life and reduce the resource burden on hospitals.